Anthocyanins Counteract Cancer Cell Survival Through Excessive Autophagy Activation
Introduction
Anthocyanins, a class of natural pigments found in plants, provide many fruits and vegetables with brilliant colors and are known for their health-promoting properties, including antioxidant, anti-inflammatory, and anticancer effects. One anthocyanin called Dracorhodin, derived from the fruit of Daemonorops draco, also known as 'dragon's blood,' has exhibited promising anticancer effects in preclinical studies. However, the molecular mechanisms underlying Dracorhodin's antitumor activities remain poorly defined.
Methods
Here, we explored whether a synthetic derivative of Dracorhodin called Dracorhodin Perchlorate (DP) could induce cytotoxic autophagy, a cellular self-digestion process, in colorectal cancer cells using techniques like confocal microscopy, calcium imaging, cell biology, and immunocytochemistry.
Results
We found DP potently suppressed colorectal cancer cell SW480 proliferation by excessively activating autophagy. Further analysis revealed DP triggered autophagy by inhibiting the mammalian target of rapamycin (mTOR) signaling, activating the autophagy regulator transcription factor EB (TFEB), enhancing lysosome expression and function, and mobilizing calcium stores to induce calcium-dependent autophagy.
Conclusion
Overall, this study provides insight into Dracorhodin’s anticancer potential by delineating specific mechanisms of cytotoxic autophagy induction via coordinated effects on mTOR-TFEB and calcium signaling. These findings pave the way for further exploration of Dracorhodin and its derivatives as potential chemotherapeutic agents through exploitation of lethal autophagy induction in cancer cells.